Home MAPK MEK inhibitor - Autophagy activator - Apoptosis related activator Trametinib (GSK1120212) For research use only.

Trametinib (GSK1120212)

Synonyms: JTP-74057

Trametinib (GSK1120212, JTP-74057) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Trametinib activates autophagy and induces apoptosis.

Trametinib (GSK1120212) Chemical Structure

Trametinib (GSK1120212) Chemical Structure

CAS No. 871700-17-3

Purity & Quality Control

Trametinib (GSK1120212) Related Products

Signaling Pathway

MEK Signaling Pathways

MEK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MDA-MB-231, SW480 and SW1116 cells Function assay 100 nM 24 h trametinib could decrease YAP levels and inhibit LMB-induced YAP upregulation in MDA-MB-231, SW1116 and SW480 cells 30833665
RG7388-resistant U87MG cells Function assay 10 nM 24 h DMSO Trametinib treatment reduced the invasive phenotype of RG7388 resistant cells. 30274984
BJAB cells Function assay 0.01μM 24 h 0.01 μM trametinib effectively suppressed the ERK hyperactivation in BJAB cells caused by the combined treatment of BKM120 and Danusertib. 30947576
Human PDAC cell lines (MIA-PACA, PANC-1, CFPAC-1, PL45, CAPAN-2 and HPAF-II) Function assay 10 nM or 100 nM 3-days or 6-days The concentration of 10 nM trametinib consistently produced significant differences between gefitinib and trametinib alone compared to combination gefitinib and trametinib in all four sensitive cell lines (CFPAC-1, pl45, CAPAN-2 and HPAF-II). No additive effect was observed in the gefitinib insensitive or excitatory cell lines (MIA-Paca and PANC-1) 30921351
Transitional cell carcinoma (TCC) cell lines Function assay 25 nM 6-24 h Canine TCC cell lines are sensitive to MEK inhibition 31048548
COLO205 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
HT-29 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
COLO205 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
MV522 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
HT-29 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
MV522 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
NCI-H727 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
NCI-H727 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
SW1417 Growth inhibition assay 72 h IC50 = 0.003 μM ChEMBL
SW1417 Growth inhibition assay 72 h IC50 = 0.003 μM ChEMBL
Calu6 Growth inhibition assay 72 h IC50 = 0.003 μM ChEMBL
LS1034 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
SW1463 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
SW1463 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
Calu6 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
LS1034 Growth inhibition assay 72 h IC50 = 0.005 μM ChEMBL
RKO Growth inhibition assay 72 h IC50 = 0.005 μM ChEMBL
NCI-H508 Growth inhibition assay 72 h IC50 = 0.008 μM ChEMBL
KM12 Growth inhibition assay 72 h IC50 = 0.01 μM ChEMBL
A427 Growth inhibition assay 72 h IC50 = 0.01 μM ChEMBL
NCI-H1155 Growth inhibition assay 72 h IC50 = 0.01 μM ChEMBL
HCT8 Growth inhibition assay 72 h IC50 = 0.014 μM ChEMBL
MDA-MB-175-VII Growth inhibition assay 72 h IC50 = 0.016 μM ChEMBL
A549 Growth inhibition assay 72 h IC50 = 0.016 μM ChEMBL
RKO Growth inhibition assay 72 h IC50 = 0.018 μM ChEMBL
NCI-H23 Growth inhibition assay 72 h IC50 = 0.02 μM ChEMBL
A427 Growth inhibition assay 72 h IC50 = 0.022 μM ChEMBL
KM12 Growth inhibition assay 72 h IC50 = 0.023 μM ChEMBL
NCI-H508 Growth inhibition assay 72 h IC50 = 0.023 μM ChEMBL
MDA-MB-231 Growth inhibition assay 3 days GI50 = 0.025 μM ChEMBL
SW837 Growth inhibition assay 72 h IC50 = 0.025 μM ChEMBL
SW480 Growth inhibition assay 72 h IC50 = 0.026 μM ChEMBL
NCI-H1355 Growth inhibition assay 72 h IC50 = 0.027 μM ChEMBL
NCI-H23 Growth inhibition assay 72 h IC50 = 0.029 μM ChEMBL
EFM19 Growth inhibition assay 72 h IC50 = 0.03 μM ChEMBL
T84 Growth inhibition assay 72 h IC50 = 0.03 μM ChEMBL
A549 Growth inhibition assay 72 h IC50 = 0.034 μM ChEMBL
NCI-H1792 Growth inhibition assay 72 h IC50 = 0.035 μM ChEMBL
SW480 Growth inhibition assay 72 h IC50 = 0.037 μM ChEMBL
COR-L23 Growth inhibition assay 72 h IC50 = 0.037 μM ChEMBL
SW1573 Growth inhibition assay 72 h IC50 = 0.038 μM ChEMBL
Calu3 Growth inhibition assay 72 h IC50 = 0.039 μM ChEMBL
HCC827 Growth inhibition assay 72 h IC50 = 0.04 μM ChEMBL
HOP62 Growth inhibition assay 72 h IC50 = 0.05 μM ChEMBL
NCI-H1355 Growth inhibition assay 72 h IC50 = 0.052 μM ChEMBL
NCI-H1792 Growth inhibition assay 72 h IC50 = 0.053 μM ChEMBL
HCT8 Growth inhibition assay 72 h IC50 = 0.055 μM ChEMBL
T84 Growth inhibition assay 72 h IC50 = 0.061 μM ChEMBL
SW900 Growth inhibition assay 72 h IC50 = 0.072 μM ChEMBL
SW837 Growth inhibition assay 72 h IC50 = 0.074 μM ChEMBL
DLD1 Growth inhibition assay 72 h IC50 = 0.093 μM ChEMBL
MDA-MB-175-VII Growth inhibition assay 72 h IC50 = 0.096 μM ChEMBL
SW900 Growth inhibition assay 72 h IC50 = 0.127 μM ChEMBL
Calu3 Growth inhibition assay 72 h IC50 = 0.158 μM ChEMBL
COR-L23 Growth inhibition assay 72 h IC50 = 0.329 μM ChEMBL
DLD1 Growth inhibition assay 72 h IC50 = 0.632 μM ChEMBL
Click to View More Cell Line Experimental Data

Biological Activity

Description Trametinib (GSK1120212, JTP-74057) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Trametinib activates autophagy and induces apoptosis.
Features More potent than PD0325901 or AZD6244.
Targets
MEK1 [1]
(Cell-free assay)		 MEK2 [1]
(Cell-free assay)
0.92 nM 1.8 nM
In vitro
In vitro

GSK1120212 inhibits the phosphorylation of MBP regardless of the isotype of Raf and MEK, with IC50 ranging from 0.92 nM to 3.4 nM. GSK1120212 demonstrates no inhibition of the kinase activities of c-Raf, B-Raf, ERK1 and ERK2. In addition, GSK1120212 does not show drastic inhibitory activity against the other 98 kinases. GSK1120212 displays potent inhibitory activity against human colorectal cancer cell lines. HT-29 and COLO205 cells, which are known to have a constitutively active B-Raf mutant, are most sensitive to GSK1120212 with IC50 0.48 nM and 0.52 nM, respectively. The cell lines bearing a K-Ras mutation show a wide range of sensitivity to GSK1120212 with IC50 of 2.2-174 nM. In contrast, COLO320 DM cells, bearing the wild-type gene in both B-Raf and K-Ras, are found to be resistant to GSK1120212 even at 10 μM. GSK1120212 treatment for 24 hours induces cell-cycle arrest at the G1 phase in all sensitive cell lines. Consistently, GSK1120212 treatment leads to upregulation of p15INK4b and/or p27KIP1 in most of the colorectal cancer cell lines. GSK1120212 inhibits constitutive ERK phosphorylation in all sensitive cell lines. GSK1120212 induces apoptosis both in HT-29 and COLO205 cells, but that COLO205 cells are more sensitive to GSK1120212 than HT-29 cells in terms of apoptosis induction. [1] GSK1120212 blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs). [2]
Kinase Assay Raf-MEK-ERK cascade kinase assay
Non-phosphorylated myelin basic protein (MBP) is coated onto an ELISA plate, and the active form of B-Raf/c-Raf is mixed with unphosphorylated MEK1/MEK2 and ERERK2 in 10 μM ATP and 12.5 mM MgCl2 containing MOPS buffer in the presence of various concentrations of GSK1120212. The phosphorylation of MBP is detected by the anti-phospho-MBP antibody.
Cell Research Cell lines HT-29, HCT-15, HCT116, COLO205, LS-174T, SW480, SW620, T84, LoVo and COLO320
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 3 or 4 days
Method

Exponentially growing cells are precultured in 96-well tissue culture plates for 24 hours and then exposed to GSK1120212. Cell growth is determined by an in vitro toxicology assay kit, sulforhodamine B based. For apoptosis assay, both floating and adherent cells are collected and fixed with 70% ethanol. After washing with PBS, the cells are suspended in 100 μg/mL RNase and 25 μg/mL propidium iodide (PI) and incubated at 37 °C for 30 minutes in the dark. The DNA content of each single cell is determined using the flow cytometer Cytomics FC500 or Guava EasyCyte plus.
Experimental Result Images Methods Biomarkers Images PMID
Western blot ERRα / IDH3 / c-Myc / Cyclin D1 pERK /ERK / pS6 / S6 β-catenin 30185207
Growth inhibition assay Cell proliferation MTT assay 30185207
Immunofluorescence phospho-PR(S345) β-catenin 29237804
In Vivo
In vivo

Oral administration of GSK1120212 at 0.3 mg/kg or 1 mg/kg once daily for 14 days is effective in inhibiting the HT-29 xenograft growth, and 1 mg/kg of GSK1120212 almost completely blocks the tumor increase. The phosphorylation of ERK1/2 is completely inhibited in the established tumor tissues by single oral dose of 1 mg/kg GSK1120212, and both p15INK4b and p27KIP1 protein levels are upregulated after 14 days of treatment with GSK1120212. In the COLO205 xenograft model, tumor regression is observed even at a dose of 0.3 mg/kg. At a dose of 1 mg/kg, a complete regression is obtained in 4 out of 6 mice in which the tumor degenerates to the point that tumor volume is not measurable. [1] Administration of GSK1120212 at 0.1 mg/kg almost completely suppresses adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) in Lewis rats or DBA1/J mice, respectively. [2]
Animal Research Animal Models Female BALB/c-nu/nu mice inoculated subcutaneously with HT-29 or COLO205 cells
Dosages ~1 mg/kg/day
Administration Orally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05275374 Not yet recruiting
Cancer|BRAF V600 Mutation|Melanoma|Colorectal Cancer|Thyroid Cancer|Nonsmall Cell Lung Cancer
Xynomic Pharmaceuticals Inc.
 December 2024 Phase 1|Phase 2
NCT06098872 Not yet recruiting
Arteriovenous Malformations
University Health Network Toronto
 November 2023 Phase 2
NCT05907304 Recruiting
Advanced or Metastatic Solid Tumors
Erasca Inc.
 August 17 2023 Phase 1
NCT05874414 Recruiting
Cholangiocarcinoma
Genfit
 August 21 2023 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 615.39 Formula

C26H23FIN5O4
CAS No. 871700-17-3 SDF Download Trametinib (GSK1120212) SDF
Smiles CC1=C2C(=C(N(C1=O)C)NC3=C(C=C(C=C3)I)F)C(=O)N(C(=O)N2C4=CC=CC(=C4)NC(=O)C)C5CC5
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 8 mg/mL ( (12.99 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
Could you help us with the best way to prepare Trametinib for in vivo i.p. injections?

Answer:
S2673 can be dissovled in 4% DMSO/corn oil at 3 mg/ml clearly.

Question 2:
How to solve the problem that this product didn't dissolve up to 10mM in DMSO at room temperature?

Answer:
The solution can be heated up to 50 degree to help dissolve. Besides, sonication (with a probe sonicator) also helped greatly.

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